title: Induction of apoptosis by 15d-PGJ2 via ROS formation: an alternative pathway without PPARγ activation in non-small cell lung carcinoma A549 cells.
abstract: Cyclopentenone prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), which is generated from the dehydration of PGD(2), is a natural ligand of peroxisome proliferator-activated receptor gamma (PPARγ) and a potential apoptotic mediator. The synthetic PPARγ ligands, troglitazone and ciglitazone, inhibit tumor progression in many cells by PPARγ activation, but the mechanism of 15d-PGJ(2) is still unclear. In this study, GW9662, an antagonist of PPARγ, and quercetin, a natural antioxidant, were used to study the apoptotic mechanism of 15d-PGJ(2) in A549 cells. Results showed that 15d-PGJ(2) induced apoptosis, which was associated with the production of reactive oxygen species (ROS) and the decrease of GSH levels. Furthermore, quercetin reduced the activity of caspases in 15d-PGJ(2)-induced apoptotic processes. These results suggest that 15d-PGJ(2) induces apoptosis in A549 cells mainly through the formation of ROS; it does not depend on PPARγ activation. Moreover, these findings support the use of quercetin and PPARγ agonists in non-small cell lung carcinoma.
authors.affiliation: Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan, ROC. paul@mail.ncku.edu.tw
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Oi-Tong
authors.initials: OT
authors.lastname: Mak
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C477819:15-deoxyprostaglandin J2; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D011794:Quercetin; D020169:Caspases; D005978:Glutathione; D015230:Prostaglandin D2; C039671:ciglitazone